Related Experiment Video
Updated: Jul 19, 2025
Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
Published on: May 10, 2022
Integrated single-cell and bulk sequencing analyses with experimental validation identify the prognostic and
1Department of Gastroenterology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei Province, People's Republic of China.
Purpose:
CD226 (DNAM-1) is an activating receptor mainly expressed in CD8 + and NK cells. CD226 deficiency and blockade have been shown to impair tumor suppression, while enhanced CD226 expression positively correlated with the increased efficacy of immune checkpoint blockade (ICB) therapies. However, the detailed function and role of CD226 in pan-cancer are largely unknown and require further in-depth investigation. Therefore, this study aims to investigate the biological functions of CD226, its role in tumor immunity, and its potential to predict prognosis and immunotherapy response in pan-cancer.
Methods:
By taking advantage of single-cell and bulk sequencing analyses, we analyzed the expression profile of CD226, its correlation with patient prognosis, immune infiltration level, immune-related genes, tumor heterogeneity, and stemness in pan-cancer. We also investigated the biological functions of CD226 using gene set enrichment analysis (GSEA) and evaluated its predictive value in response to immunotherapy and small-molecule targeted drugs. In addition, we validated the expression of CD226 in tumor-infiltrating CD8 + and NK cells and studied its association with their functions using a murine B16F10 melanoma model.
Results:
CD226 exhibited differential expression across most tumor types, and its elevated expression was associated with improved clinical outcomes in multiple cancer types. CD226 is closely correlated with numerous tumor-infiltrating immune cells, tumor stemness, and heterogeneity in most cancers. Furthermore, based on single-cell sequencing analysis, CD226 expression was found to be higher on effector CD4 + T cells than naïve CD4 + T cells, and its expression level was decreased in exhausted CD8 + T cells relative to effector CD8 + T cells in multiple cancer types. Additionally, flow cytometric analysis demonstrated that CD226 was highly correlated with the function of tumor-infiltrating NK and CD8 + T cells in murine B16F10 melanoma. Moreover, GSEA analysis revealed that CD226 was closely associated with T cell activation, natural killer cell mediated immunity, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. Finally, CD226 showed promising predictive potential for responsiveness to both ICB therapies and various small-molecule targeted drugs.
Conclusion:
CD226 has shown great potential as an innovative biomarker for predicting patient prognosis, immune infiltration levels, and the function of tumor-infiltrating CD8 + T cells, as well as immunotherapy response. Additionally, our findings suggest that the optimal modification of CD226 expression and function, combined with current ICBs, could be a promising strategy for tumor immunotherapy.
Insights
CD226 enhances anti-tumor immunity and predicts immunotherapy response across cancers. Targeting CD226 shows promise for improving cancer treatment strategies.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- CD226 (DNAM-1) is an activating receptor on CD8+ T and NK cells.
- CD226 deficiency impairs tumor suppression; enhanced expression correlates with better immune checkpoint blockade (ICB) efficacy.
- The pan-cancer role of CD226 in immunity and therapy response remains largely unexplored.
Purpose of the Study:
- Investigate CD226's biological functions and role in tumor immunity.
- Determine CD226's potential as a biomarker for prognosis and immunotherapy response in pan-cancer.
- Explore CD226's association with immune cell function and therapeutic drug response.
Main Methods:
- Analyzed CD226 expression, prognosis correlation, immune infiltration, tumor heterogeneity, and stemness using single-cell and bulk sequencing.
- Performed gene set enrichment analysis (GSEA) for functional insights.
- Validated CD226 expression and function in tumor-infiltrating CD8+ T and NK cells using a murine melanoma model.
Main Results:
- CD226 expression varied across cancers, with higher levels linked to better outcomes.
- CD226 correlated with immune infiltration, stemness, and heterogeneity.
- Single-cell analysis revealed CD226 expression differences on T cell subsets; it was associated with T cell activation, NK cell immunity, and cytotoxicity.
- CD226 predicted response to ICB and targeted therapies.
Conclusions:
- CD226 is a potential biomarker for prognosis, immune infiltration, CD8+ T cell function, and immunotherapy response.
- Modulating CD226 expression and function alongside ICBs offers a promising strategy for cancer immunotherapy.
More Related Videos
10:29Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
08:30Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018